Mechanism analysis of food factors for prevention of diabetes complications

• Project/Area Number: 24500986
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Eating habits, studies on eating habits
• Research Institution: Shubun University (2017); Nagoya University (2014-2016); Kyoto Prefectural University of Medicine (2012-2013)
• Principal Investigator: OYA-ITO TOMOKO 修文大学, 健康栄養学部, 准教授 (80329648)
• Project Period (FY): 2012-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2016: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2015: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 糖尿病合併症 / メチルグリオキサール / プロテオミクス解析 / 翻訳後修飾 / 糖化反応 / メイラード反応 / ペルオキシレドキシン6 / 酸化ストレス

Outline of Final Research Achievements

Methylglyoxal (MG) is an endogenous highly reactive dicarbonyl degradation product and forms stable adducts primarily with arginine (Arg) and lysine (Lys) residues. An antioxidant protein peroxiredoxin 6 (Prx6) was found as the major MG-adducted protein in red blood cells from diabetic patients. Peroxidase activity of Prx6 was inhibited by MG modification. Mass spectrometry analysis of peptide fragments of MG-modified Prx6 identified Arg and Lys residues as the modification sites. Specially, identified Arg-132 is situated in the catalytic center of peroxidase activity. These results suggest that the decrease in peroxidase activity is due to modification of active-site residues in Prx6. The level of MG modification on Prx6 was correlated to both fasting- and postprandial- glucose in diabetic patients. Moreover, this level was higher in the hyperlipidomia patients. Therefore, it was suggested that MG modification plays an important role in the development of diabetic complications.

Research Products

• [Journal Article] High-resolution copy number variation analysis of schizophrenia in Japan. (2017)
  • Author(s): Kushima I, Aleksic B, Nakatochi M, Shimamura T, Shiino T, Yoshimi A, Kimura H, Takasaki Y, Wang C, Xing J, Ishizuka K, Oya-Ito T, Nakamura Y, Arioka Y, Maeda T, Yamamoto M, Yoshida M, Noma H, Hamada S, Morikawa M, Uno Y, Okada T, Iidaka T, Iritani S, Yamamoto T,
  • Journal Title: Molecular Psychiatry Volume: 22 Issue: 3 Pages: 430-440
  • DOI: 10.1038/mp.2016.88
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Resequencing and Association Analysis of Six PSD-95-Related Genes as Possible Susceptibility Genes for Schizophrenia and Autism Spectrum Disorders (2016)
  • Author(s): Xing J, Kimura H, Wang C, Ishizuka K, Kushima I, Arioka Y, Yoshimi A, Nakamura Y, Shiino T, Oya-Ito T, Takasaki Y, Uno Y, Okada T, Iidaka T, Aleksic B, Mori D, Ozaki N.
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 27491-27491
  • DOI: 10.1038/srep27491
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mutation screening of GRIN2B in schizophrenia and autism spectrum disorder in a Japanese population. (2016)
  • Author(s): Takasaki Y, Koide T, Wang C, Kimura H, Xing J, Kushima I, Ishizuka K, Mori D, Sekiguchi M, Ikeda M, Aizawa M, Tsurumaru N, Iwayama Y, Yoshimi A, Arioka Y, Yoshida M, Noma H, Oya-Ito T, Nakamura Y, Kunimoto S, Aleksic B, Uno Y, Okada T, Ujike H, Egawa J, Kuwabara H, Someya T, Yoshikawa T, Iwata N, Ozaki N
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 33311-33311
  • DOI: 10.1038/srep33311
  • Peer Reviewed / Open Access
• [Journal Article] Investigation of Rare Single-Nucleotide PCDH15 Variants in Schizophrenia and Autism Spectrum Disorders (2016)
  • Author(s): Ishizuka, K., H. Kimura, C. Wang, J. Xing, I. Kushima, Y. Arioka, T. Oya-Ito, Y. Uno, T. Okada, D. Mori, B. Aleksic, and N. Ozaki.
  • Journal Title: PLoS One Volume: 11 Issue: 4 Pages: e0153224-e0153224
  • DOI: 10.1371/journal.pone.0153224
  • Peer Reviewed / Open Access
• [Journal Article] Association study of BCL9 gene polymorphism rs583583 with schizophrenia and negative symptoms in Japanese population. (2015)
  • Author(s): Kimura H, Tanaka S, Kushima I, Koide T, Banno M, Kikuchi T, Nakamura Y, Shiino T, Yoshimi A, Oya-Ito T, Xing J, Wang C, Takasaki Y, Aleksic B, Okada T, Ikeda M, Inada T, Iidaka T, Iwata N, Ozaki N.
  • Journal Title: Scientific reports Volume: 5 Issue: 1 Pages: 15705-15705
  • DOI: 10.1038/srep15705
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] he combined effect of acetylation and glycation on the chaperone and anti-apoptotic functions of human α-crystallin. Biochim Biophys Acta (2013)
  • Author(s): Nahomi RB, Oya-Ito T, Nagaraj RH
  • Journal Title: -Molecular Basis of Disease Volume: vol. 1832、No.1 Issue: 1 Pages: 195-203
  • DOI: 10.1016/j.bbadis.2012.08.015
  • Peer Reviewed
• [Journal Article] Hemopexin is upregulated in rat intestinal mucosa injured by indomethacin (2012)
  • Author(s): Takagi T, Naito Y, Okada H, Takaoka M, Oya-Ito T, Yamada S, Hirai Y, Mizushima K, Yoshida N, Kamada K,Katada K, Uchiyama K, Ishikawa T, Handa O, Yagi N, Konishi H, Kokura S, Ichikawa H, Yoshikawa T
  • Journal Title: J Gastroenterol Hepatol Volume: J Gastroenterol Hepatol Issue: s3 Pages: 70-75
  • DOI: 10.1111/j.1440-1746.2012.07076.x
  • Peer Reviewed
• [Journal Article] The role of methylglyoxal-modified proteins in gastric ulcer healing. (2012)
  • Author(s): Takagi T, Naito Y, Oya-Ito T, Yoshikawa T.
  • Journal Title: Curr Med Chem. Volume: 19(1) Pages: 137-144
  • Peer Reviewed
• [Journal Article] Exercise-induced muscle damage impairs insulin signaling pathway associated with IRS-1 oxidative modification. (2012)
  • Author(s): Aoi W, Naito Y, Tokuda H, Tanimura Y, Oya-Ito T, Yoshikawa T.
  • Journal Title: Physiol Res. Volume: 61(1) Pages: 81-88
  • Peer Reviewed
• [Journal Article] Detection of N.EPSILON.-(hexanoyl)lysine in the tropomyosin 1 protein in N-methyl-N'-nitro-N-nitrosoguanidine-induced rat gastric cancer cells (2011)
  • Author(s): Okada H, Naito Y, Takagi T, Osawa,T
  • Journal Title: Journal of Clinical Biochemistry and Nutrition Volume: 50 Issue: 1 Pages: 47-52
  • DOI: 10.3164/jcbn.11-39
  • NAID: 130004466669
  • ISSN: 0912-0009, 1880-5086
  • Peer Reviewed
• [Presentation] Methylglyoxal modification of peroxiredoxin 6 as a biomarker for diabetic complications (2018)
  • Author(s): Tomoko Oya-Ito, Yuji Naito, Tomohisa Takagi, Keisuke Shima, Yoshito Itoh, and Toshikazu Yoshikawa
  • Organizer: 13th International Symposium on the Maillard Reaction
  • Int'l Joint Research
• [Presentation] Heat shock protein 27 (Hsp27)の翻訳後修飾解析と細胞生物学的な意義検証 (2018)
  • Author(s): 大矢友子
  • Organizer: 第３回日本医用マススペクトル学会西部会
• [Presentation] Methylglyoxal-modified peroxiredoxin 6 as a biomarker for diabetic complications (2017)
  • Author(s): Tomoko Oya-Ito, Yuji Naito, Tomohisa Takagi, Keisuke Shima, Yoshito Itoh, and Toshikazu Yoshikawa
  • Organizer: 16th Human Proteome Organization World Congress
  • Int'l Joint Research
• [Presentation] The development of molecular diagnostic tool for schizophrenia using lymphoblastoid cell lines (2016)
  • Author(s): Akira Yoshimi, Shohko Kunimoto, Branko Aleksic, Akihiro Hirakawa, Yuko Arioka, Tomoko Oya-Ito, Itaru Kushima, Yukako Nakamura, Tomoko Shiino, Daisuke Mori, Takuji Maeda, Satoshi Tanaka, Shuko Hamada, Hiromi Noma, Mami Yoshida, Yukihiro Noda, Taku Nagai, Kiyofumi Yamada, Norio Ozaki et al.
  • Organizer: US HUPO 12th Annual Conference
  • Place of Presentation: Boston, USA
  • Year and Date: 2016-03-13
  • Int'l Joint Research
• [Presentation] AGEsによるシャペロン機能促進作用 (2014)
  • Author(s): 大矢友子
  • Organizer: 第24回日本メイラード学会年会
  • Place of Presentation: 熊本市国際交流会館（熊本県熊本市）
  • Year and Date: 2014-11-07 – 2014-11-08
  • Invited
• [Presentation] Intake of isoflavones attenuates the development of metabolic syndrome associated with consumption of a Western-style diet in C57BL/6J mice (2014)
  • Author(s): Tomoko Oya-Ito, Kazuhiro Katada, Mayuko Morita, Katsura Mizushima, Yasuki Higashimura, Kazuhiro Kamada, Kazuhiko Uchiyama, Osamu Handa, Tomohisa Takagi, Nobuaki Yagi, Toshikazu Yoshikawa, Yoshito Itoh, and Yuji Naito
  • Organizer: 13th World Congress of the Human Proteome Organization
  • Place of Presentation: Madrid、スペイン
  • Year and Date: 2014-10-05 – 2014-10-08
• [Presentation] Implications of methylglyoxal modification of peroxiredoxin 6 for delayed wound-healing process in diabetes. (2014)
  • Author(s): Oya-Ito T, Naito Y, Takagi T, Shima K, Ito Y, Yoshikawa T.
  • Organizer: 17th Biennial Meeting of Society for Free Radical Research International.
  • Place of Presentation: Kyoto
• [Presentation] Intake of isoflavones alleviate metabolic syndrome associated with consumption of a Western-style diet in C57BL/6J mice. (2014)
  • Author(s): Oya-Ito T, Katada K, Morita M, Mizushima K, Higashimura Y, Kamada K, Uchiyama K, Handa O, Takagi T, Yagi N, Yoshikawa T, Itoh Y, Naito Y.
  • Organizer: 17th Biennial Meeting of Society for Free Radical Research International.
  • Place of Presentation: Kyoto
• [Presentation] Quercetin attenuates the development of non-alcoholic fatty liver disease in mice via the decrease in oxidative stress and glycation. (2014)
  • Author(s): Katada K, Oya-Ito T, Morita M, Mizushima K, Higashimura Y, Kamada K, Uchiyama K, Handa O, Takagi T, Yagi N, Yoshikawa T, Itoh Y, Naito Y.
  • Organizer: 17th Biennial Meeting of Society for Free Radical Research International.
  • Place of Presentation: Kyoto
• [Presentation] 糖尿病合併症におけるペルオキシレドキシン6のメチルグリオキサール修飾による失活機構の解析 (2013)
  • Author(s): 大矢友子、内藤裕二、髙木智久、島 圭介、吉川敏一
  • Organizer: 第66回日本酸化ストレス学会
  • Place of Presentation: 名古屋
• [Presentation] 消化管疾患における糖化反応 (2013)
  • Author(s): 大矢友子、内藤裕二、吉川敏一
  • Organizer: 第13回日本抗加齢医学会総会
  • Place of Presentation: 横浜
  • Invited
• [Presentation] Implications of methylglyoxal modification of Peroxiredoxin 6 for impaired healing in diabetic wound. (2013)
  • Author(s): Oya-Ito T, Naito Y, Takagi T, Shima K, Yoshikawa T.
  • Organizer: The 12th Human Proteome Organisation World Congress (HUPO 2013)
  • Place of Presentation: Yokohama
• [Presentation] Relevance of methylglyoxal modification of peroxiredoxin 6 to the development of diabetic complications. (2013)
  • Author(s): Oya-Ito T, Naito Y, Takagi T, Shima K, Ito Y, Yoshikawa T.
  • Organizer: Society for Free Radical Biology and Medicine's 20th Annual Meeting.
  • Place of Presentation: San Antonio, U.S.A.
• [Presentation] αクリスタリンのシャペロン機能と抗アポトーシス機能のメチルグリオキザール修飾による増強作用 (2012)
  • Author(s): 大矢 友子、Ram H. Nagaraj 、内藤 裕二、吉川 敏一
  • Organizer: 第65回日本酸化ストレス学会
  • Place of Presentation: あわぎんホール徳島県郷土文化会館（徳島）
• [Presentation] Post-translational modification of Peroxiredoxin 6 in gastric ulcer in diabetic mice. (2012)
  • Author(s): Oya-Ito T, Naito Y, Takagi T, Shima K, Yoshikawa T.
  • Organizer: The 33rd Naito Conference
  • Place of Presentation: シャトレーゼ ガトーキングダム サッポロ（北海道）
• [Presentation] Methylglyoxal modification of peroxiredoxin 6. (2012)
  • Author(s): Oya-Ito T, Naito Y, Takagi T, Shima K, Yoshikawa T.
  • Organizer: Human Proteome Organisation (HUPO) 2012 11th Annual World Congress
  • Place of Presentation: John B. Hynes Veterans Memorial Convention Center (Boston, USA)
• [Presentation] Post-translational modification of Peroxiredoxin 6 in ulcer of diabetic mice. (2012)
  • Author(s): Oya-Ito T, Naito Y, Takagi T, Shima K, Yoshikawa T.
  • Organizer: 11th International Symposium on the Maillard Reaction
  • Place of Presentation: University of Lorraine (Nancy, France)
• [Presentation] αクリスタリンのメチルグリオキザール修飾によるシャペロン機能と抗アポトーシス機能の増強作用 (2012)
  • Author(s): 大矢 友子、Ram H. Nagaraj 、内藤 裕二、吉川 敏一
  • Organizer: 第22回日本メイラード学会年会
  • Place of Presentation: 東京農工大学小金井キャンパス（東京）
• [Presentation] 糖尿病合併症の指標としての血中ペルオキシレドキシン6の メチルグリオキサール修飾
  • Author(s): 大矢友子、内藤裕二、髙木智久、島 圭介、伊藤義人、吉川敏一
  • Organizer: 第23回日本メイラード学会学術集会
  • Place of Presentation: 大阪
• [Book] 分子精神医学 (2016)
  • Author(s): 大矢 友子、尾崎 紀夫
  • Total Pages: 81
  • Publisher: 先端医学社
• [Book] 臨床化学 (2014)
  • Author(s): 大矢友子、中村由嘉子、吉見 陽、尾崎紀夫
  • Total Pages: 351
  • Publisher: （株）エム・シー・アイ
• [Book] Heat Shock Proteins. Classification, Functions and Applications. (2013)
  • Author(s): Oya-Ito T, Naito Y, Takagi T, Handa O, Shima K, Yoshikawa T.
  • Total Pages: 12
  • Publisher: Nova Science Publishers, Inc.
• [Remarks] 名古屋大学大学院医学系研究科 精神医学分野
  • URL: http://www.med.nagoya-u.ac.jp/seisin/graduateschool/research.html
• [Remarks] 京都府立医科大学ホームページ
  • URL: http://www.kpu-m.ac.jp/
• [Remarks] 京都府立医科大学消化器内科学教室、先端医療と研究について
  • URL: http://www.f.kpu-m.ac.jp/k/sun/sentan/index.html